Ding Xiao, Ma Yun, Li Shicheng, Liu Jingze, Qin Luyao, Wu Aiping
State Key Laboratory of Common Mechanism Research for Major Diseases, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, 100 Chongwen Road, Industrial Park District, Suzhou 215123, Jiangsu, China.
Key Laboratory of Pathogen Infection Prevention and Control (Peking Union Medical College), Ministry of Education, 16 Tianrong Street, Daxing District, Beijing 102629, China.
Brief Bioinform. 2025 May 1;26(3). doi: 10.1093/bib/bbaf233.
Genomic reassortment is a key driver of influenza virus evolution and a major factor in pandemic emergence, as reassorted strains can exhibit significantly altered antigenicity. However, due to technical and ethical constraints, research on reassortment patterns (RPs) has been limited, impeding effective surveillance and control strategies. To address this gap, we developed FluRPId, a framework for identifying RPs based on the genetic diversity of influenza viruses. FluRPId integrates principles of reassortment diversity maximization, dominance, and epidemiological likelihood to assess the credibility of detected reassortment events. Applying FluRPId, we constructed a comprehensive reassortment landscape of influenza viruses, encompassing widespread reassortment events with high credibility, which also include most previously reported reassortment events. Our analysis revealed that the NS gene frequently reassorts with PA and NA, while reassortment involving HA, NA, and NS occurs more frequently than expected. Furthermore, we identified specific loci combinations that exhibit strong linkage during reassortment, providing insights into segment association preferences. Additionally, extensive reassortment chains were observed across all subtypes, underscoring the continuity of reassortment in influenza virus evolution. Notably, we identified significant cross-species reassortment events and characterized host adaptation changes in cross-species-transmitted viruses. Our study provides the most comprehensive reassortment landscape of influenza viruses to date, uncovering key patterns, preferences, and evolutionary continuity. These findings bridge a critical gap in macro-scale reassortment studies and offer insights for future research and control efforts.
基因组重配是流感病毒进化的关键驱动因素，也是大流行出现的主要因素，因为重配毒株可能表现出显著改变的抗原性。然而，由于技术和伦理限制，对重配模式（RPs）的研究一直有限，这阻碍了有效的监测和控制策略。为了填补这一空白，我们开发了FluRPId，这是一个基于流感病毒遗传多样性识别RPs的框架。FluRPId整合了重配多样性最大化、优势性和流行病学可能性的原则，以评估检测到的重配事件的可信度。应用FluRPId，我们构建了一个全面的流感病毒重配图谱，涵盖了具有高可信度的广泛重配事件，其中也包括大多数先前报道的重配事件。我们的分析表明，NS基因经常与PA和NA重配，而涉及HA、NA和NS的重配比预期更频繁地发生。此外，我们确定了在重配过程中表现出强连锁的特定基因座组合，从而深入了解片段关联偏好。此外，在所有亚型中都观察到了广泛的重配链，强调了流感病毒进化中重配的连续性。值得注意的是，我们确定了重大的跨物种重配事件，并对跨物种传播病毒中的宿主适应性变化进行了表征。我们的研究提供了迄今为止最全面的流感病毒重配图谱，揭示了关键模式、偏好和进化连续性。这些发现填补了宏观尺度重配研究中的关键空白，并为未来的研究和控制工作提供了见解。
